Adequate coronary vasodilation is essential to myocardial perfusion imaging. Coronary vasodilation increases coronary blood flow. This increase creates differences in the distribution of the imaging agent great enough to identify regions supplied by stenosed coronary vessels and to distinguish problem areas from healthy tissue.
Exercise stress testing often is employed for dilating coronary vessels, hence increasing coronary blood flow. However, maximum exercise levels are often required for sufficient vasodilation, and exercise capacity varies greatly among patients. Many patients absolutely cannot exercise to any satisfactory level, due to peripheral vascular disease, medications, poor patient motivation, and a variety of other coexisting conditions. Therefore, exercise may not always be an option.
The compound adenosine, having the formula C10H13N5O4, is known to be highly efficacious as a pharmacologic stress agent for myocardial imaging in patients which are unable to exercise adequately. This compound has consistently produced maximum vasodilation of coronary arteries, with relatively minimal side effects. Adenosine is typically administered intravenously to a patient at rest, and its pharmacological action then mimics some degree of physical assertion. The short half-life of adenosine is responsible for its short-acting pharmacological effects, making it extremely useful for diagnostic evaluation and risk assessment in coronary artery disease. The attending physician can quickly image the diseased coronary area, and thereafter the adenosine and any adjunct compounds are broken down or evacuated from the body.
Other adenosine-based analogs and derivatives have now shown great potential as possible coronary vasodilators for use in medical imaging. Many of these compounds have been set forth and identified in U.S. Pat. No. 6,232,297. This patent sets forth a new class of 2-alkynyladenosine derivatives.
Unfortunately, many adenosine derivatives can be very difficult to solubilize in aqueous media. There are also long-range stability issues associated with adenosine-based formulations. To address this issue, the skilled artisan has often turned to solvents like glycerol, propylene glycol and other polar additives when preparing injection solutions. Alternatively, β-cyclodextrin, because of its unique donut-shape, has been shown to form inclusion complexes with sparingly soluble and unstable drugs. The action of β-cyclodextrin significantly stabilizes and increases the water-solubility of many pharmacological compounds.
U.S. Pat. No. 6,407,079 describes many β-cyclodextrin derivatives which are set forth as being particularly useful as complex forming agents to solubilize and stabilize active compounds. These include hydroxyethyl, hydroxypropyl and dihydroxypropyl ether, their corresponding mixed ethers, and further mixed ethers with methyl or ethyl groups, such as methyl-hydroxyethyl, methyl-hydroxypropyl, ethyl-hydroxyethyl and ethyl-hydroxypropyl ether of β-cyclodextrin.
However, stability issues may still persist with one or more of these compounds. What is therefore needed in the art is an improved composition containing one or more adenosine derivatives, together with a suitable solvent, that is highly useful in myocardial perfusion imaging, and is also storage stable for extended periods. Also needed in the art is a method for enhancing cardiovascular imaging by administering an improved cardiovascular stress formulation to a patient.